Spheroids are 3D multi-cell aggregates formed in non-addherent culture conditions. In ovarian cancer (OC), they serve as a vehicle for cancer cell dissemination in the peritoneal cavity. We investigated genes and networks upregulated in three dimensional (3D) versus two-dimensional (2D) culture conditions by Affymetrix gene expression profiling and identified ALDH1A1, a cancer stem cell marker as being upregulated in OC spheroids. Network analysis confirmed ALDH1A1 upregulation in spheroids in direct connection with elements of the -catenin pathway. A parallel increase in the expression levels of -catenin and ALDH1A1 was demonstrated in spheroids vs. monolayers an in successive spheroid generations by using OC cell liness and primary OC cells. The percentage of Aldefluor positive cells was significantly higher in spheroids vs. monolayers in IGROV1, A2780, SKOV3, and primary OC cells. B-catenin knock-down decreased ALDH1A1 expression and chromatin immunoprecipitation demonstrated that -catenin directly binds to the ALDH1A1 promoter. Both siRNA mediated -catenin knock-down and a novel ALDH1A1 small molecule enzymatic inhibitor described here for the first time, decreased the number of OC spheroids (p<0.001) and cell viability. These data strongly support the role of -catenin regulated ALDH1A1 in the maintenance of OC spheroids and of a stem cell phenotype and propose new ALDH1A1 inhibitors targeting this cell population.
β-Catenin-regulated ALDH1A1 is a target in ovarian cancer spheroids.
Specimen part
View SamplesIn polygenic disorders we do not know exactly, how many genes are involved in the pathomechanism, but the analysis of fetal gene expression can get us closer to the solution. In our study we were searching for the genetic background of the polygenic neural tube defect, which is the second most common birth defect in the world (1 in 1000 live births). Our data revealed novel candidate genes, like SLAP, LST1 and BENE, which can play an important role in the pathogenesis of neural tube defects. We created a data warehouse from the results, suitable for further analysis. This study also demonstrates that a routinely collected amount of amniotic fluid (as small as 6 mL) is enough to successfully hybridize isolated RNA to expression arrays, making the ability to use the technique from normally collected amniotic fluid samples.
Use of routinely collected amniotic fluid for whole-genome expression analysis of polygenic disorders.
Specimen part, Disease, Disease stage
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genome wide mapping reveals PDE4B as an IL-2 induced STAT5 target gene in activated human PBMCs and lymphoid cancer cells.
Specimen part, Cell line
View SamplesIdentify IL-2 mediated genes in Kit225 cells.
Genome wide mapping reveals PDE4B as an IL-2 induced STAT5 target gene in activated human PBMCs and lymphoid cancer cells.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The IL-4/STAT6 signaling axis establishes a conserved microRNA signature in human and mouse macrophages regulating cell survival via miR-342-3p.
Specimen part, Cell line
View SamplesRAW264.7 mouse macrophages were transfected with negative control and miR-342-3p mimics and subjected to microarray analysis 18 hours after the transfection.
The IL-4/STAT6 signaling axis establishes a conserved microRNA signature in human and mouse macrophages regulating cell survival via miR-342-3p.
Specimen part, Cell line
View SamplesIn order to gain insights into how PPARg regulates different facets of dendritic cell (DC) differentiation, we sought to identify PPARg regulated genes and gene networks in monocyte-derived dendritic cells using global gene expression profiling. We employed an exogenous ligand activation approach using a selective PPARg ligand (rosiglitazone abbreviated as RSG). In addition, we have defined culture conditions in which human serum (HS) induces PPARg activation via a yet uncharacterized endogenous mechanism. We also compared the gene expression profile of developing dendritic cells obtained from patients harboring dominant negative mutations of the PPARg receptor (C114R and C131Y).
PPARgamma regulates the function of human dendritic cells primarily by altering lipid metabolism.
Sex, Specimen part
View SamplesPurpose: RNA-Seq analysis can help identify large set of differentially expressed genes at a time. We performed RNA-Seq analysis to identify differentially expressed genes in the PBMCs of war veterans suffering from PTSD. Methods: Total RNA from PBMCs from PTSD +ve and -ve individuals were used for RNA-Seq analysis. Results: We obtained, on average, ~60 millions reads per sample. More than 70% of the reads were mapped to human genome. Functional analysis of the differentially expressed genes (362) revealed dysregulation in immune system network. Conclusions: Our present study provides further proof that immune system related genes and pathways are dysregulated in PTSD PBMCs. Overall design: RNA-Seq was performed with RNA from 5 each control and PTSD individuals. PBMCs collected within one hour of blood draw were used for RNA isolation. 1 ug of total RNA was used for library synthesis and sequenced in a HighSeq 2000 illumina instrument at Tufts University.
Decreased AGO2 and DCR1 in PBMCs from War Veterans with PTSD leads to diminished miRNA resulting in elevated inflammation.
Specimen part, Subject
View SamplesComparison of gene expression level of 3T3-L1, PMEF and ES cell derived adipocytes to eWAT samples.
Highly efficient differentiation of embryonic stem cells into adipocytes by ascorbic acid.
Specimen part
View SamplesCD14+ human monocytes differentiating into DCs in the presence of IL4 and GM-CSF were treated with agonists for RXR and its partners or vehicle 18 hours after plating (experiment with RXR and permissive partners, donor 1-3) or 14 hours after plating (experiment with nonpermissive partners, donor 4-6). Cells were harvested 12 hours thereafter. Experiments were performed in biological triplicates representing samples from three different donors.
Research resource: transcriptome profiling of genes regulated by RXR and its permissive and nonpermissive partners in differentiating monocyte-derived dendritic cells.
Specimen part, Subject
View Samples